Does Compazine Cause Respiratory Depression?
Compazine (prochlorperazine) can cause respiratory depression, but this is not its primary adverse effect and occurs less commonly than its extrapyramidal and cardiovascular side effects. 1
Primary Adverse Effects of Prochlorperazine
The most clinically significant adverse effects of prochlorperazine include:
- Hypotension - This is the most common serious complication reported in clinical use 1
- Extrapyramidal effects - Including restlessness, akathisia, dystonic reactions, pseudo-parkinsonism, and tardive dyskinesia 1
- Neuroleptic malignant syndrome - A rare but life-threatening complication 1
- Cardiovascular effects - Tachycardia and arrhythmias may occur 1
Respiratory Depression Risk Profile
While respiratory depression is listed as a potential adverse effect, the evidence suggests it is not a prominent or common complication:
In a large series of 764 patients receiving droperidol (a related phenothiazine derivative) as an adjunct to endoscopic sedation, hypotension was the most common complication and no patient experienced respiratory depression requiring ventilatory support 1
Research comparing chlorpromazine (a closely related phenothiazine) to other sedatives in patients with chronic airways obstruction found that 50 mg intramuscular chlorpromazine caused significant respiratory depression in only 3 of 8 patients studied 2
Paradoxically, prochlorperazine has been shown to stimulate ventilatory response to hypoxia and can actually reverse morphine-induced respiratory depression in research settings 3, 4
Clinical Context and Risk Factors
Respiratory depression from prochlorperazine is most likely to occur in specific high-risk scenarios:
Overdose situations - The FDA label notes that CNS depression to the point of somnolence or coma can occur in overdose, with potential respiratory difficulty from extrapyramidal involvement causing dysphagia 5
Combination with other CNS depressants - When used in sedation cocktails (such as the meperidine-promethazine-chlorpromazine mixture mentioned in ASA guidelines), delayed drug absorption and slow elimination may contribute to residual sedation and cardiorespiratory depression 1
Patients with limited respiratory reserve - Those with chronic lung disease or debility are at higher risk for acute respiratory failure from any CNS-depressant drug 6
Key Clinical Pitfalls to Avoid
Do not assume prochlorperazine carries the same respiratory depression risk as opioids or benzodiazepines - It does not have specific reversal agents like naloxone or flumazenil, and its respiratory effects are minimal compared to these drug classes 1
Monitor primarily for hypotension and extrapyramidal reactions - These are far more common and clinically significant than respiratory depression 1
Be cautious with combination regimens - When prochlorperazine is used with opioids or benzodiazepines in sedation protocols, the synergistic CNS depression may prolong recovery time and increase cardiorespiratory risk 1
Maintain airway vigilance in overdose - While respiratory depression is not the primary concern, extrapyramidal involvement can produce dysphagia and respiratory difficulty requiring airway protection 5
Bottom Line for Clinical Practice
Prochlorperazine's risk profile is dominated by hypotension and extrapyramidal side effects, not respiratory depression. 1 When used at standard antiemetic doses (25 mg orally or rectally), respiratory compromise is uncommon. However, appropriate monitoring and airway management capabilities should be available when using any CNS-active medication, particularly in combination sedation regimens or in patients with compromised respiratory reserve. 1, 6